REMS: When Approval Comes With Conditions

A Risk Evaluation and Mitigation Strategy (REMS) is a safety program FDA can require as a condition of approval, where the agency concludes that labeling alone is not enough to keep a product's benefits ahead of its risks.

FDA has had this authority since the FDA Amendments Act of 2007. A REMS can include enrolment systems, certification of prescribers and pharmacies, documented safe-use conditions, and periodic assessments showing the program meets its goals.

The elements

Medication Guide or patient package insert. Information FDA requires to reach the patient directly.

Communication plan. Materials directed at healthcare providers, such as letters to professional societies.

Elements to Assure Safe Use (ETASU). The tier that changes how a product is distributed. Any of:

• Prescribers must be specially certified.
• The product is dispensed only in certain settings, such as a hospital.
• Dispensing requires evidence of safe-use conditions, such as a documented laboratory result.
• Each patient is subject to monitoring.
• Each patient is enrolled in a registry.

Implementation system. How the sponsor monitors and enforces the ETASU across the distribution chain.

Timetable for submission of assessments. You report to FDA on whether the REMS is meeting its goals.

Commercial consequences

An ETASU REMS changes who can prescribe your product and where it can be dispensed. That affects uptake, the sales model, and the burden on a prescriber choosing between your product and one without a REMS.

The registry, the certification program and the assessment reporting continue for as long as the REMS does.

Modification and removal

Sponsors can propose modifications to a REMS, and FDA can require them. Where post-marketing experience shows the risk is better understood or the program is not adding safety, a REMS can be reduced or released entirely, and many have been.

Shared system REMS

Where a REMS applies to a class, generic applicants may be required to join a single shared system rather than operate a parallel one. This has been a recurring source of dispute, because access to the brand's REMS materials can become a barrier to generic entry, and Congress addressed it in the CREATES Act.